We have previously demonstrated in rats that exposure to a simulated altitude of 18,000 feet resulted in hemoglobinemia, hepatic metabolic derangements and possible impairment of renal function. The mechanisms and etiology of these pathophysiological problems of altitude-exposed rats will be investigated. An enhanced "ineffective hematopoiesis" and/or a depressed catabolism of hemoglobin are proposed as the possible mechanisms for the genesis of hemoglobinemia, and will be studied by analyzing the early labeled bilirubin, early labeled carbon monoxide and early labeled plasma hemoglobin following injection of C14-2-glycine, and by measuring the rate of hemoglobin catabolism, plasma clearance and tissue uptake of Fe59-hemoglobin. By means of a bile fistula and a hepatic venous catheter, hepatic blood flow, oxygen consumption, and BSP and bilirubin excretion will be measured to evaluate further the functional state of the liver. The contributing roles of polycythemia and hypoxia will also be assessed in this study. Inulin clearance will be measured to evaluate renal function, and the possible roles of polycythemia, hemoglobinemia and hypoxia on this measurement will also be evaluated. The existence of a possible altitude threshold for the pathogenesis of these problems will be explored. The induction of hepatic and renal heme oxygenase and the change in the total activity of splenic heme oxygenase will be measured in conjunction with exposure to different altitudes as well as with different durations of exposure to 18,000 feet, in order (1) to clarify the specific role of this enzyme in adaptation to high altitude, (2) to evaluate the "two system" hypothesis of hemoglobin conversion and (3) to demonstrate the deleterious effect of severe hypoxia on the liver and kidney.